1. Field of the Invention
The present invention relates to pellets having a gastric juice-resistant active compound matrix.
2. Discussion of the Background
WO 01/68058 describes pharmaceutical forms formulated to be gastric juice-resistant. The pharmaceutical forms are essentially constructed from a core containing a pharmaceutical active compound, an inner coating of a copolymer or a mixture of copolymers which comprises 85 to 98% by weight of free radical-polymerized C1- to C4-alkyl esters of acrylic or of methacrylic acid and 15 to 2% by weight of (meth)acrylate monomers having a quaternary ammonium group in the alkyl radical and an outer coating of a copolymer which comprises 75 to 95% by weight of free-radical polymerized C1- to C4-alkyl esters of acrylic or of methacrylic acid and 5 to 25% by weight of (meth)acrylate monomers having an anionic group in the alkyl radical.
US 2005/0191352 describes the production of extrudates containing pharmaceutical active compounds having controlled release of active compound by means of melt extrusion. In addition to the active compound, the mixtures to be extruded can contain polymers such as, for example, Eudragit® RS, Eudragit® NE or mixtures of these polymers. The extrusion preferably takes place in a twin-screw extruder. The extrudates discharged can be comminuted and shaped in the hot state by means of rotating knives to give cylindrical or alternatively to give spherical, ellipsoidal or lenticular particles. The active compound-containing particles thus obtained can be further processed, e.g. by filling into capsules, to give multiparticulate pharmaceutical forms.
EP 1 563 897 A1 describes a device for the production of rounded pellets (pelletizer). The device consists of an upstream feed arrangement, for shapable material which is in particular fed from an extruder and a housing having a rotating cutting unit for cutting the material into material sections, and means for generating a stream of gas in the housing, by the action of which the material sections collide with a housing wall, undergoing rounding. Preferably, the housing wall is cooled in order to reduce the material removed. The device is suitable in particular for the production of pellets for the pharmaceutical sector by mixing pharmaceutical excipients, such as, for example, polymers, with at least one pharmaceutical active compound in the extruder, the extrudates emerging through a nozzle in the cutter housing and being comminuted and rounded by die-face cutting with gas cooling to give pellets.
WO 96/14058 describes melt-extruded oral opioid formulations. Mixtures of the active compound oxycodone HCl, Eudragit® RS, Eudragit® L and stearic acid, for example, are proposed. According to Example 13, the corresponding proportions of the four substances can be 25.0/48.75/3.75 and 22.5%. The substances are first mixed, subsequently extruded at about 83° C. in an extruder, fed to a pelletizer, comminuted to give pellets of about 1.5 mm and then filled into capsules. Formulation according to Example 13 already releases 20% of the active compound contained after 2 h in artificial gastric juice and is therefore not gastric juice-resistant. In artificial intestinal juice, the active compound is released continuously with a delay, such that after 8 h at pH 7.5 approximately 44% of the active compound is released.
Pharmaceutical forms having gastric juice-resistant coatings, such as are known, for example, from WO 01/68058 have drawbacks. For example, the pharmaceutical form described in WO 01/68058 is complex in its production due to its layer structure.